SAT-440 Modulating Effects of Progesterone on Spontaneous and Ghrelin-Induced GH Secretion in Postmenopausal Women

Abstract

Introduction. GH secretion is regulated by hypothalamic neuropeptides, sex steroids, and negative feedback signals across the lifespan. GH secretion in premenopausal women is higher than that in age-matched men, and can be amplified by oral estradiol (E2) in postmenopausal (PM) women. In contrast, the effect of progesterone (P) on GH secretion has rarely been studied in the presence or absence of estrogen repletion. Study design: Four parallel groups of PM women (total 40) received (1) im saline and oral placebo, (2) im saline and oral micronized P (3x200mg/day), (3) E2 im (5 mg) and oral placebo, and (4) E2 im and oral P, respectively. Study parameters were overnight (10 h) and ghrelin-stimulated (0.3 µg/kg) GH secretion. Results: Mean E2 levels increased to 88 and 99 pg/mL and mean P to 10.1 and 20.3 ng/dL. Whereas E2 at this dose did not change GH, P vs placebo reduced pulsatile GH secretion to 7.20±2.14 µg/L/10h vs 9.58±1.97 (P=0.045). Mean GH concentrations and burst amplitudes were respectively 0.97±0.31 and 1.52±0.29 (P=0.025), and 2.76±1.04 and 3.95±0.90 (P=0.031). Visceral fat area, determined by CT, was a strongly negative GH predictor of pulsatile GH secretion, R=-0.53 (P=0.001, β=-0.096±0.026). P levels correlated negatively with GH secretion, with or without AVF or E2 in the regression equation (e.g. pulsatile GH secretion: R=-0.69, P=0.005, β=0.693±0.246). P administration also reduced ghrelin-stimulated GH release (9.6±1.9 vs 7.2±2.1 µg/L, P=0.046). Restricting this analysis to estrogen-treated subjects, P decreased ghrelin-stimulated GH secretion from 10.7±2.7 to 2.6±1.3 µg/L/2 h (P=0.002) in a P concentration-dependent manner, viz., R=-0.49 (P=0.04, β=-0.040±0.018). Conclusions. Early follicular phase E2 levels did not impact spontaneous or ghrelin-stimulated GH concentrations, whereas P inhibited 10-h overnight and 2-h ghrelin-stimulated GH secretion a concentration-dependent fashion. Accordingly, the physiological significance of P on GH regulation requires further studies.